Source

• Surface tension is inversely proportional to the surfactant concentration per unit area.

Causes of hemidiaphragmatic elevation

[!INFO] From radiopaedia

The fibers transmitting visual information from the superior retina remain superior in the chiasm; those from the inferior retina remain inferiorly situated. Approximately 90% of chiasmal fibers originate from the macula, and, of these, those that cross lie superiorly and posteriorly within the chiasm.
Source

Source

Source

Q 7: Craniopharyngioma

• A craniopharyngioma is a slow-growing, extra-axial, epithelial-squamous, calcified, and cystic tumor arising from remnants of the craniopharyngeal duct and/or Rathke cleft and occupying the sellar/suprasellar region. They are histologically benign but have malignant behaviour.
• I.e they tend to recur after apparent total resection
• and invade surrounding structures.
• Most commonly they occur in the pituitary stalk.
• Arise from remnants of Rathke's pouch.
• Symptoms: hypopituitarism and visual defects.
  

1. CRH stimulation test - differentiates Cushing's disease from all other causes of hypercortisolism

• Lithium is used for prophylaxis of mania in bipolar patients. Not for acute treatment.
• For acute mania, antipsychotics and antiepileptics are equally effective.
  Pharmacology:
  • Dose titrations are done weekly.
  • Once steady state concentrations are reached, levels are checked every 3 months.
• 

  • Effect of duration of lithium accumulation

    • Acute toxicity: GI symptoms predominate (N/V/D) and neurologic symptoms are delayed.
    • Acute on chronic toxicity : Similar to acute toxicity.
    • Chronic toxicity: Early and predominant neurologic signs. (agitation, confusion, slurred speech) superimposed on complications of chronic use (neuromuscular irritability, tremor)

  • Side effects occuring at therapeutic range:

    • (plasma level > 1.5mmo/L) - GI: N/V/D and neuromuscular: Course tremor, weakness, ataxia, blurred vision
    • Medical emergency: hyperreflexia, hyperextension of limbs, convulsions, syncope, coma and death.
    • Hypotension refractory to fluids
    • Life threatening arrhythmias
    • Cardiopulmonary collapse

  • Drugs interfering with renal excretion of lithium: Thiazides >> loop diuretics, ACEi, ARB, NSAIDS,

    • Inhibits thyroxine release from the gland and peripheral conversion.

  • The syndrome of irreversible lithium-effectuated neurotoxicity (SILENT): prolonged neurologic and neuropsychiatric features which may not resolve despite stopping lithium.

  • Lithium is teratogenic -> Ebsteins anomaly.

Folate and B12 metabolism

[[DNAFolateB12Deficiency.png]]

Source

[!INFO] Key points:

1. The synthesis of methionine from homocysteine is catalyzed by methionine synthase, an enzyme that requires not only folate (as 5-methyltetrahydrofolate) but also vitamin B12.
2. 3 vitamins are interlinked : B12, B9 and B6
3. Thus, the concentration of homocysteine in the blood is regulated by three B-vitamins: folate, vitamin B12, and vitamin B6

| Folate | B12 |
| :--------------------------------------------------------------------------------------------------------------: | :-------------------------------------------------------------------------------------------------------------------------: |
| green leaves (mnemonic: folate = foliage) | Animal sources |
| 4 months of stores | 2 years of stores |
| large percentage destroyed in cooking | Only little destroyed in cooking |
| Absorption is mainly in the duodenum and jejunum Source | Terminal ileum by receptor mediated endocytosis. Source |

• Low intake or increased demand (high cell turnover states, pregnancy)
  • Haemolytic anaemia, alcoholism, pregnancy, lactation, dialysis can cause ⬇folate levels.
• Folate deficiency may cause
  1. glossitis, diarrhoea and depression and megaloblastic anaemia indistinguishable from that of B12 deficiency. Source
  2. patchy hyperpigmentation (dosal surfaces of fingers and toes)
  3. Low grade feverSource
• Providing only folic acid supplementation to a patient who has cobalamin deficiency may lead to development of irreversible neuropathies.
  
  • Anti tuberculosis drugs (INH, Ethambultol and pyrazinamide, ?not rifampicin)
  • Sulfonamides DO NOT inhibit human folate metabolism. [[antibiotics|Sulphonamides]]
  • For high dose MTX treatment, folinic acid, a reduced form of folate is given. This bypasses the need for dihydrofolate reductase. (folinic acid is also called leucovorin)

• RNA virus of the picornavirus family.
• Relatively resistant to heat and acid but kill by boiling for 1 minute and by formaldehyde, chlorine and UV radiation.
  • Important because low cost sanitation practices can prevent transmission.
• IM formaldehyde-inactivated vaccine is used for prevention.

Presentation

• Incubation period is 4 weeks.
  • The virus only replicates in hepatocytes but is present in blood and shed in faeces.
• Symptoms begin with flu like non specific symptoms.
• Then dark urine followed by pale stool and icterus. (i.e obstructive picture)
  • icterus is less common in children.
• Onset of icterus heralds a rapid decrease in infectivity
• Initial response is IgM (which persists for about 3 months); Then class switching occurs to IgG which persists indefinitely and confers immunity.

Labs:

• Direct hyperbilirubinaemia. (Older individuals have higher bilirubin levels) Source
• Rise in liver enzymes (AST > ALT, Levels can exceed 10,000)
• Can have hypoalbuminaemia.
• Gold standard for diagnosis is nucleid acid amplification test.
• Usual diagnosis is by IgM which becomes positive with the onset of symptoms.
  

Management

• Self limited. Supportive management.
• Few progress to fulminant hepatic failure -> poor prognosis.
• Few can go on to have protracted "relapsing" disease.

Urea is elevated in acute dehydration.
Mechanism: Source

[!INFO] Shortcuts

• For PAH : clearance = renal blood flow.
• For inulin: Clearance = GFR

Side effects of Erythropoietin treatment:

1. • accelerated hypertension potentially leading to encephalopathy and seizures (blood pressure increases in 25% of patients)

• bone aches
• flu-like symptoms
• skin rashes, urticaria
• pure red cell aplasia* (due to antibodies against erythropoietin)
• raised PCV increases risk of thrombosis (e.g. Fistula)
• iron deficiency 2nd to increased erythropoiesis

There are a number of reasons why patients may fail to respond to erythropoietin therapy:

• iron deficiency
• inadequate dose
• concurrent infection/inflammation
• hyperparathyroid bone disease
• aluminium toxicity
  • Aluminum toxicity is a systemic disorder observed in patients on hemodialysis and occasionally in patients who have severe chronic kidney disease. It occurs due to aulminium in dialysis fluid and in aluminium containing phosphate binders. It is rare in resource rich settings because these sources have been eliminated.
  • Features: osteomalacia, iron resistant microcytic anaemia, hypercalcemia etc.

• usually a remarkably well tolerated drug.
• However, crystals can precipitate and cause nephropathy. Prevented by adequate hydration.
• Neurotoxicity is rare but can cause delirium, tremors, hallucinations and if severe delerium and coma.
• Neurologic symptoms occuring in a patient who has just been started on dialysis or has missed several dialysis sessions.
• Occurs due to rapid reduction in plasma osmolality due to removal of urea by dialysis leading to cerebral oedema.
• Symptoms include : headache, nausea, blurred vision, confusion, and if severe, stupor, seizures and coma.
• Clinical diagnosis: No test.
• Prevention: Prevening exccessive clearance of BUN during dialysis.
• Treatment:: Modifying the dialysis prescription.

[!INFO] Mnemonic:
Poor penetration : BAT CAVE (deep dark corners = poor penetrance)

• Beta lactams
• Aminoglycosides
• Tetracyclines
• Clindamycin
• Amphotericin
• antiretroViral (tenofovir)
• Echinocandins and other antifungals

Cephalosporins:

• According to the 2016 Sri lanka antibiotic guidelines, cephalosporins like ceftriaxone and cefotaxine can be used for meningitis.

• Depressed mental status
• Decreased respiratory rate
• Decreased tidal volume
• Decreased bowel sounds
• Miotic (constricted) pupils
  | Toxin | Antidote | |
  | --------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------ |
  | Acetaminophen | N-Acetylcysteine | |
  | Anticholinergics | Physostigmine* | |
  | Anticoagulants, oral factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) | Andexanet alfa | |
  | Benzodiazepines | Flumazenil* | |
  | Black widow spider bite | Lactrodectus antivenom | |
  | Botulism | Botulinum antitoxin | |
  | Beta-blockers | Glucagon, IV lipid emulsion | |
  | Calcium channel blockers | Calcium
  IV insulin in high doses with IV glucose
  IV lipid emulsion | |
  | Carbamates | Atropine Pralidoxime chloride | |
  | Crotaline snake bites (US) | Crotalinae polyvalent immune Fab (ovine) | |
  | Cyanide | Hydroxocobalamin Cyanide antidote kit (includes amyl nitrate, sodium nitrite, and sodium thiosulfate) | Vit B12 forms cyanocobalamin which restores mitochondrial function |
  | Dabigatran | Idarucizumab | |
  | Digitalis glycosides (eg, digoxin, digitoxin, oleander, foxglove) | Digoxin-specific Fab fragments | Fab = Antigen binding fragments |
  | Ethylene glycol | Fomepizole Ethanol | [[2021 General Medicine July#Methanol poisoning]] (alcohol dehydrogenase inhibitor) |
  | Heavy metals | Chelating drugs (see table Guidelines for Chelation Therapy) | heavy metals: Dimercaprol (aka British anti-lewisite)
  Cobalt, Pb, Zn : Edetate calcium sodium
  Au,Pb,AS : Penicillamine
  Succimer |
  | Ionizing radiation | Potassium iodide | |
  | Iron | Deferoxamine | |
  | [[Tuberculosis#Isoniazid|Isoniazid]] | Pyridoxine (vitamin B6) | Pyridoxine (B6) |
  | Methanol | Fomepizole Ethanol | Prevents formation of glycolic acid and glycloxylic acid by alcohol dehydrogenase. |
  | Methemoglobin-forming agents (eg, aniline dyes, some local anesthetics, nitrates, nitrites, phenacetin, sulfonamides, dapsone). | Methylene blue
  Exchange transfusion
  Hyperbaric oxygen
  | Hb has Fe3+ instead of 2+. (poor O2 capacity).
  Blue Skin.
  Dark blood. |
  | Methotrexate | Leucovorin (folinic acid) Glucarpidase (carboxypeptidase-G2) | |
  | Opioids | Naloxone | |
  | Organophosphates | Atropine, Pralidoxime | See above |
  | Scorpion envenomation (Centruroides sp) | Centruroides immune F(ab’)2 | |
  | Sulfonylurea | Octreotide | Somatostatin analog; prevents calcium entry into beta cells -> inhibits insulin release. Prevents rebound hypoglycemia in sulfonylurea overdose. |
  | Thallium | Prussian blue | |
  | Tricyclic antidepressants | Sodium bicarbonate | |
  | Unfractionated heparin | Protamine | |
  | Valproic acid | L-Carnitine† | |
  | Warfarin | Vitamin K
  Fresh frozen plasma Prothrombin complex concentrate (PCC) | |

#2021BSQ-NOV/Q54
Aporecaeruloplasmin + 6 Cu atoms = ceruloplasmin (the major circulating form of Copper)

Mutations in ATP7B in Wilson disease impairs both the incorporation of copper into apoceruloplasmin and the excretion of copper into bile.

• Impaired incorporation of copper into ceruloplasmin leads to misfolding of the protein and shorter plasma half life. This reduces serum caeruloplasmin level.
• Serum copper levels are usually lower than normal.
  • Because of deficiency of ceruloplasmin in the serum.
  • Accumulation of non ceruloplasmin bound free copper causes copper deposition in other organs.
• Release of large amounts of copper into the blood due to hepatic necrosis can cause haemolysis.
• Haemolysis + liver disease => think of Wilson's.
  Diagnosis

• KF rings are absent in early disease; therefore, absense doesn't rule out disease. Although they can be visible unaided, proper assessment requires a slit lamp examination.
• Serum ceruloplasmin levels are normal in upto 10%. (i.e poor sensitivity)
• Urine copper measurement is a good diagnostic test.
• Liver: histology alone is unreliable, Biopsy samples need to be quantitatively measured for copper content; This is the gold standard test.

[!TIP] Eyes and basal ganglia and of course liver

• Histologic demonstration of copper requires rhodanine stain;
• Acute / chronic hepatitis -> The presentation in children.
  • Most patients have underlying advanced fibrosis or cirrhosis and can have episodes of acute hepatitis.
• basal ganglia [[striatumBasalGanglia.png]] -> Cavitation -> tremmor, dysarthria, ataxia, dementia and dystonia and behavioral disturbances; The presentation in young adults. (Typically early 20s)
  • Dystonia eventually leads to severe deformities.
• Renal tubules -> tubular degeneration
• Bones -> erosions
• Eyes -> Kayser Fleischer ring. (requires slit lamp)
• Treatment: Zinc acetate as first line, lifetime penicillamine, trientine and zinc acetate for asymptomatic cases.
• heart: Wilson't usually doesn't affect the heart.

Source
Foscarnet and cidofovir are toxic.

Source

See [[Anaemia#Folate and B12 metabolism]]

• Downward lens dislocation (as opposed to upward in marfans)
• 
• Pes excavatum, Pes carinatum, genu valgum
• Intellectual disability (learning difficulty)
• Signs and symptoms of strokes.
  • Homocystaenaemia is a related condition which presents with early strokes.
• caused by a deficiency of the enzyme cystathionine beta synthase. (or others)
  • There are 3 types of homocystinuria.
• In Down's syndrome, there is excessive activity of cystathionine beta synthase.
• Cyanide-nitroprusside test is positive. It is done on the urine to detect sulfur containing amino acids; Not sensitive or specific.
• Blood levels for homocysteine can be done. Samples must be transported on ice and spun within 1 hour.
  Source
• Nephropathic cystinosis is an inherited (autosomal recessive) lysosomal storage disorder caused by defective transport of the amino acid cystine out of lysosomes. The stored cystine is poorly soluble and crystallizes within the lysosomes of many cell types, leading to widespread tissue and organ damage.